1997 Abstracts The American Pediatric Society and The Society for Pediatric Research | Published:

Mast Cells Mediate Acute Inflammatory Responses to Implanted Blomaterials.• 679

Despite widespread use of implantable devices, tissue-contact implants often trigger adverse responses such as inflammation, thrombosis, infection and fibrosis. We have focused our work on biomaterial-mediated inflammatory responses because chronic inflammation is associated with degradation and failure of many types of tissue implants. We earlier found that the attraction of phagocytes to implant surfaces requires precedent adsorption of host fibrin(ogen); phagocyte accumulation does not occur on implants in hypofibrinogenemic (ancrod-treated) mice unless the implant is pre-coated with purified fibrinogen (J. Exp. Med. 178:2147, 1993; J. Clin. Invest. 97: 1329, 1996). However, the signalling mechanisms whereby adsorbed fibrinogen might trigger recruitment of phagocytes remain unknown. Because histamine promotes rapid immigration of inflammatory cells to sites of tissue injury or antigen-antibody complex formation, we hypothesized that histamine might be critical in the recruitment of inflammatory cells to biomaterial implants. Using a previously established animal model involving the intraperitoneal implantation of polyethylene terephthalate disks in mice, we find: (i) Mast cells within mesenteric tissue adjacent short-term intraperitoneal implants are extensively degranulated, suggesting mast cell activation as an early response. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists greatly diminishes recruitment of both neutrophils (<20% of control) and monocyte/macrophages (<30% of control) to implants. (iii) The likely source of histamine release is mast cells; congenitally mast cell-deficient mice (WBB6F1-/-) exhibit markedly reduced accumulation of both neutrophils (control = 162,000 ± 49,000 cells/cm2; mast cell-deficient = 67,000 ± 11,000/cm2) and monocytes/macrophages(control = 366,000 ± 63,000; mast cell-deficient = 79,000 ± 19,000; [n = 5], p<0.01) on intraperitoneal implants. We conclude that mast cells and their granular products, especially histamine, are important in the recruitment of inflammatory cells to biomaterial implants. Improved knowledge of the genesis of such responses may, in future, permit design of more biocompatible implanted devices.

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